title: Remifentanil preconditioning reduces hepatic ischemia-reperfusion injury in rats via inducible nitric oxide synthase expression.
abstract: BACKGROUND
  Opioid preconditioning against ischemia reperfusion injury has been well studied in myocardial and neuronal tissues. The objective of this study was to determine whether remifentanil could attenuate hepatic injury and to investigate the mechanisms.
  
  
  METHODS
  A rat model of hepatic ischemia reperfusion injury and a hepatocyte hypoxia reoxygenation (HR) injury model were used, respectively, in two series of experiments. Remifentanil was administered before ischemia or hypoxia and the experiments were repeated with previous administration of naloxone, L-arginine and N-ω-nitro-L-arginine methyl ester, a nonselective opioid receptor antagonist, a nitric oxide donor, and nitric oxide synthase (NOS) inhibitor, respectively. Serum aminotransferase, cytokines, and hepatic lipid peroxidation were measured. Histopathology examination and apoptotic cell detection were assessed. For the in vitro study, cell viability, intracellular nitric oxide, apoptosis, and NOS expression were evaluated.
  
  
  RESULTS
  Remifentanil and L-arginine pretreatment reduced concentrations of serum aminotransferases and cytokines, decreased the concentrations of hepatic malondialdehyde and myeloperoxidase activity, and increased superoxide dismutase, nitric oxide, and inducible NOS expression in vivo. Decreased histologic damage and apoptosis were also seen in these two groups. These changes were prevented by previous administration of N-ω-nitro-L-arginine methyl ester but not naloxone. There was an increase in inducible NOS protein expression but not endogenous NOS in remifentanil and L-arginine pretreated groups compared with control, naloxone, and N-ω-nitro-L-arginine methyl ester groups.
  
  
  CONCLUSIONS
  Pretreatment with remifentanil can attenuate liver injury both in vivo and in vitro. Inducible NOS but not opioid receptors partly mediate this effect by exhausting reactive oxygen species and attenuating the inflammatory response.
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Yang
authors.forename: Kun-Ming
authors.initials: KM
authors.lastname: Tao
authors.forename: Yan-Tao
authors.initials: YT
authors.lastname: Liu
authors.forename: Chi-Wai
authors.initials: CW
authors.lastname: Cheung
authors.forename: Michael G
authors.initials: MG
authors.lastname: Irwin
authors.forename: Gordon T C
authors.initials: GT
authors.lastname: Wong
authors.forename: Hao
authors.initials: H
authors.lastname: Lv
authors.forename: Jian-Gang
authors.initials: JG
authors.lastname: Song
authors.forename: Fei-Xiang
authors.initials: FX
authors.lastname: Wu
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Yu
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D019194:Ischemic Preconditioning; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000378:metabolism; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077208:Remifentanil; D015427:Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D000637:Transaminases / Q000097:blood / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D016207:Cytokines; D009292:Narcotic Antagonists; D010880:Piperidines; D009270:Naloxone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000637:Transaminases; D000077208:Remifentanil